In recent decades, the demand for biomedical imaging tools has grown very rapidly as a key feature for biomedical research and diagnostic applications. Particularly, fluorescence imaging has gained increased attention as a non-invasive, inexpensive technique that allows real-time imaging. However, tissue auto-fluorescence under external illumination, together with a weak tissue penetration of low wavelength excitation light, largely restricts the application of the technique. Accordingly, new types of fluorescent labels are currently being investigated and, in this search, phosphorescent nanoparticles promise great potential, as they combine the interesting size-dependent properties of nanoscale materials with a long-lasting phosphorescence-type emission that allows optical imaging well after excitation (so avoiding autofluorescence). In this work, core-shell structures consisting of SrAlO:Eu,Dy luminescent cores encapsulated within a biocompatible silica shell were prepared, showing a green persistent phosphorescence with an afterglow time of more than 1000 s. A high-energy ball milling procedure was used to reduce the size of the starting phosphors to a size suitable for cellular uptake, while the silica coating was produced by a reverse micelle methodology that eventually allows the excitation and emission light to pass efficiently through the shell. Confocal fluorescence microscopy using HeLa cancer cells confirmed the potential of the all-ceramic composites produced as feasible labels for in vitro optical imaging.